The aim of the proposal is to determine whether drugs which inhibit collagen biosynthesis may be useful in the treatment of atherosclerotic vascular disease. The drugs that will be tested will include penicillamine and colchicine. They will be studied in the cynomolgus monkey with pre-established atherosclerosis induced by feeding a 2 percent cholesterol and 10 percent butter diet for 6 months. During the regression period, which will alst 15 months, the drugs will be fed with a low cholesterol diet and the results will be compared with those in animals fed a low cholesterol diet, alone. The extent and severity of atherosclerosis will be evaluated morphologically and biochemically and the findings will be correlated with the changes in plasma lipids and lipoproteins, ECG and regional myocardial blood flow using radioactively labeled microspheres. It is believed that the proposed correlative studies on the biochemical pathology and pathophysiology of experimental atherosclerosis will help to establish the pharmacological rationale for the use of different types of durgs in the treatment of atherosclerotic disease.